MHC class II antigens, HLA-DR in the human and Ia in the mouse, are membrane bound glycoproteins that are encoded by genes of the major histocompatibility complex. Expression of these antigens is of great functional importance for the initiation and perpetuation of immune responses. In a number of immunopathologic conditions HLA-DR antigen negative cells are stimulated to express class II antigens. In these cases an immunologic role has been postulated for the class II antigen expression. During the past year, we have determine if class II antigens are expressed in certain diseases and we have evaluated their possible role in autoimmune and inflammatory diseases. Initial studies identified cells in the anterior segment and cells in the retina (rpe cell) which express class II antigens during inflammatory eye disease. Treatment with monoclonal anti-Ia antibodies diminished the clinical disease and the expression of MHC class II antigens. These studies have been extended to evaluate Sjogren's syndrome. We found that the salivary gland in Sjogren's syndrome is infiltrated predominantly by T-lymphocytes and that this is associated with class II antigen expression on glandular epithelial cells. Moreover, we evaluated the effect of cyclosporin A on the immunopathological lesions in Sjogren's syndrome. We found that cyclosporin treatment resulted in decrease in both T cell infiltration and a decrease in HLA-DR antigen expression. These studies on MHC class II antigen expression in localized autoimmune diseases provide evidence that the activation of these antigens may contribute to the immunopathogenesis of these disease.